TY - JOUR
T1 - Eculizumab Safety
T2 - Five-Year Experience From the Global Atypical Hemolytic Uremic Syndrome Registry
AU - Rondeau, Eric
AU - Cataland, Spero R.
AU - Al-Dakkak, Imad
AU - Miller, Benjamin
AU - Webb, Nicholas J.A.
AU - Landau, Daniel
N1 - Funding Information:
Medical writing and editorial support were funded by Alexion Pharmaceuticals, Inc. The sponsor and investigators thank the patients and their families for their participation in and support for this clinical study. The authors would like to acknowledge Peloton Advantage, LLC, an OPEN Health Company, which provided editorial and medical writing support by Kristen W. Quinn, PhD, and Envision Pharma Inc, which provided medical editing support by Kersten Reich, MPH, and Linda V. Wychowski, PhD, with funding from Alexion Pharmaceuticals, Inc.ClinicalTrials.gov identifier:NCT01522183. This analysis was funded by Alexion Pharmaceuticals, Inc. Boston, MA. Alexion Pharmaceuticals, Inc. was responsible for the collection, management, and analysis of information contained in the Global aHUS Registry. Alexion Pharmaceuticals, Inc. contributed to data interpretation, preparation, review, and approval of the manuscript for submission. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication. Qualified academic investigators may request participant-level, de-identified clinical data and supporting documents (statistical analysis plan and protocol) pertaining to this study. Further details regarding data availability, instructions for requesting information, and our data disclosure policy will be available on the Alexion.com website (http://alexion.com/research-development).
Publisher Copyright:
© 2019 International Society of Nephrology
PY - 2019/11/1
Y1 - 2019/11/1
N2 - Introduction: Eculizumab has transformed outcomes for patients with atypical hemolytic uremic syndrome (aHUS). Its efficacy and safety profile was well characterized in the clinical trial program. The long-term safety profile was not previously assessed or compared against nontreated patients in an observational registry setting. Methods: The Global aHUS Registry recruits patients with clinical diagnoses of aHUS. This analysis includes baseline characteristics and targeted safety events from adult and pediatric patients who were “ever treated” versus “never treated” with eculizumab in the first 5 years of the registry, through January 26, 2017. Results: Overall, 1321 patients (adult, n = 842; pediatric, n = 479; ever treated, n = 865; never treated, n = 456) were enrolled. A higher proportion of ever-treated versus never-treated adult and pediatric patients had renal, cardiovascular, pulmonary, central nervous system, gastrointestinal symptoms, and hepatic impairment. No differences in safety event rates between ever-treated and never-treated patients were observed, except serious infections in pediatric patients (5.15 versus 1.12 events/100 patient-years for ever- and never-treated patients, respectively). Deaths were more frequent in adult (4.7% and 9.9% of ever- and never-treated patients) compared with pediatric patients (1.8% of ever-treated patients; no deaths in never-treated patients).Three meningococcal infections were reported in ever-treated patients; 1 infection led to a fatal outcome. Conclusion: In this large observational dataset covering 5 years of registry enrollment, no new safety concerns were identified for adult or pediatric eculizumab-treated patients with aHUS, confirming a positive benefit−risk profile in a real-world setting.
AB - Introduction: Eculizumab has transformed outcomes for patients with atypical hemolytic uremic syndrome (aHUS). Its efficacy and safety profile was well characterized in the clinical trial program. The long-term safety profile was not previously assessed or compared against nontreated patients in an observational registry setting. Methods: The Global aHUS Registry recruits patients with clinical diagnoses of aHUS. This analysis includes baseline characteristics and targeted safety events from adult and pediatric patients who were “ever treated” versus “never treated” with eculizumab in the first 5 years of the registry, through January 26, 2017. Results: Overall, 1321 patients (adult, n = 842; pediatric, n = 479; ever treated, n = 865; never treated, n = 456) were enrolled. A higher proportion of ever-treated versus never-treated adult and pediatric patients had renal, cardiovascular, pulmonary, central nervous system, gastrointestinal symptoms, and hepatic impairment. No differences in safety event rates between ever-treated and never-treated patients were observed, except serious infections in pediatric patients (5.15 versus 1.12 events/100 patient-years for ever- and never-treated patients, respectively). Deaths were more frequent in adult (4.7% and 9.9% of ever- and never-treated patients) compared with pediatric patients (1.8% of ever-treated patients; no deaths in never-treated patients).Three meningococcal infections were reported in ever-treated patients; 1 infection led to a fatal outcome. Conclusion: In this large observational dataset covering 5 years of registry enrollment, no new safety concerns were identified for adult or pediatric eculizumab-treated patients with aHUS, confirming a positive benefit−risk profile in a real-world setting.
KW - atypical hemolytic uremic syndrome
KW - complement
KW - safety
KW - thrombotic microangiopathy
UR - http://www.scopus.com/inward/record.url?scp=85072020205&partnerID=8YFLogxK
U2 - 10.1016/j.ekir.2019.07.016
DO - 10.1016/j.ekir.2019.07.016
M3 - Article
C2 - 31890998
AN - SCOPUS:85072020205
SN - 2468-0249
VL - 4
SP - 1568
EP - 1576
JO - Kidney International Reports
JF - Kidney International Reports
IS - 11
ER -